This research proposal, a continuation of work now underway deals mainly with physiological control mechanisms of anterior pituitary function, with the tissue phase of thyroid hormone metabolism, and with the role of neuroendocrin factors in human diabetes. Utilizing immunoassays or bioassays and isotope incorporation methods for the releasing factors, we plan to study the mechanism of, and regulation of biosynthesis and secretion of TRH, LRH, PRF, PIF, GH RF, and Somatostatin as affected by feedback hormonal control and neurotransmitter control. These observations, taken together with studies of direct feedback effects of hormones on pituitary function will be utilized to analyze the function of the pituitary-thyroid axis, of the pituitary-gonad axis, and of the control of growth hormone and prolactin secretion. Methods suitable for human research will be used to study control of hypophysiotropic secretion under normal physiological states and in pathological states of disturbed pituitary function such as Acromegaly Diabetes and Cushing's Disease. The nature of the hypophysiotropic secretory cells in the hypothalamus will be studied by electron microscopy utilizing immunological techniques for localization of TRH and LRH. Phylogenetic studies of TRH will also be carried out. Direct assay of extracts of tissue and enzyme methods will be utilized to study mechanisms of conversion and control of T4 to T3, of the importance of these hormones in embryogenesis, in post natal adaptation, in chronically sick humans, and in relation to hypothalamic-pituitary control of TSH secretion. The importance of secretion of GH RF and of Somatostatin in acromegaly and in diabetes will be evaluated by measuring secretion of these releasing hormones.